4-16166331-C-T

Position:

• chr4-16166331-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000405303.7(TAPT1):​c.1474+302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 152,274 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (245 hom., cov: 32)
• Consequence: TAPT1 ENST00000405303.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.122

Genes affected

TAPT1 (HGNC:26887): (transmembrane anterior posterior transformation 1) This gene encodes a highly conserved protein that localizes to the centrosome and/or ciliary basal body. Mutations in this gene disrupt Golgi morphology and trafficking and normal primary cilium formation and these mutations are congenitally manifested by severe undermineralization of the intra-uterine skeleton. A mutation in the mouse ortholog of this gene results in homeotic, posterior-to-anterior transformations of the axial skeleton which are similar to the phenotype of mouse homeobox C8 gene mutants. In mouse, this gene is thought to function downstream of homeobox C8 to transduce extracellular patterning information during axial skeleton development. [provided by RefSeq, Jan 2017]

TAPT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-16166331-C-T is Benign according to our data. Variant chr4-16166331-C-T is described in ClinVar as [Benign]. Clinvar id is 1268825.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAPT1	NM_153365.3	c.1474+302G>A		intron_variant		ENST00000405303.7	NP_699196.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAPT1	ENST00000405303.7	c.1474+302G>A		intron_variant		1	NM_153365.3	ENSP00000385347.2

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6555 AN: 152156 Hom.: 243 Cov.: 32

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0258

Gnomad OTH AF: 0.0444

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0432 AC: 6571 AN: 152274 Hom.: 245 Cov.: 32 AF XY: 0.0407 AC XY: 3028 AN XY: 74456

Gnomad4 AFR AF: 0.0896

Gnomad4 AMR AF: 0.0341

Gnomad4 ASJ AF: 0.0433

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.0258

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0231 Hom.: 29

Bravo AF: 0.0469

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2271749; hg19: chr4-16167954;